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Cannabinoid agonist WIN 55,212-2 prevents the development of paclitaxel-induced peripheral neuropathy in rats. Possible involvement of spinal glial cells

Cannabinoid agonist WIN 55,212-2 prevents the development of paclitaxel-induced peripheral neuropathy in rats. Possible involvement of spinal glial cells
Cannabinoid agonist WIN 55,212-2 prevents the development of paclitaxel-induced peripheral neuropathy in rats. Possible involvement of spinal glial cells
Spinal glial activation contributes to the development and maintenance of chronic pain states, including neuropathic pain of diverse etiologies. Cannabinoid compounds have shown antinociceptive properties in a variety of neuropathic pain models and are emerging as a promising class of drugs to treat neuropathic pain. Thus, the effects of repeated treatment with WIN 55,212-2, a synthetic cannabinoid agonist, were examined throughout the development of paclitaxel-induced peripheral neuropathy. Painful neuropathy was induced in male Wistar rats by intraperitoneal (i.p.) administration of paclitaxel (1mg/kg) on four alternate days. Paclitaxel-treated animals received WIN 55,212-2 (1mg/kg, i.p.) or minocycline (15mg/kg, i.p.), a microglial inhibitor, daily for 14days, simultaneous with the antineoplastic. The development of hypersensitive behaviors was assessed on days 1, 7, 14, 21 and 28 following the initial administration of drugs. Both the activation of glial cells (microglia and astrocytes) at day 29 and the time course of proinflammatory cytokine release within the spinal cord were also determined. Similar to minocycline, repeated administration of WIN 55,212-2 prevented the development of thermal hyperalgesia and mechanical allodynia in paclitaxel-treated rats. WIN 55,212-2 treatment also prevented spinal microglial and astrocytic activation evoked by paclitaxel at day 29 and attenuated the early production of spinal proinflammatory cytokines (interleukin (IL)-1?, IL-6 and tumor necrosis factor (TNF)-?). Our results confirm changes in the reactivity of glial cells during the development of peripheral neuropathy induced by paclitaxel and support a preventive effect of WIN 55,212-2, probably via glial cells reactivity inactivation, on the development of this neuropathy.
paclitaxel, peripheral neuropathy, cannabinoid, hyperalgesia, cytokine, rat
0014-2999
Burgos, Elisa
65c07eac-d5a1-4b2d-9e01-ce7297367258
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Pascual, David
84461a39-0f01-4baf-9869-cddb1d6f95a5
Martín, María Isabel
627fcdf6-f169-475f-b7a0-9c982053efd4
Nieto-Sampedro, Manuel
6d62c63e-e900-4219-b596-447dae4b0c2d
Goicoechea, Carlos
7ed76451-ca7b-45e3-b62b-a52cc07fb450
Burgos, Elisa
65c07eac-d5a1-4b2d-9e01-ce7297367258
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Pascual, David
84461a39-0f01-4baf-9869-cddb1d6f95a5
Martín, María Isabel
627fcdf6-f169-475f-b7a0-9c982053efd4
Nieto-Sampedro, Manuel
6d62c63e-e900-4219-b596-447dae4b0c2d
Goicoechea, Carlos
7ed76451-ca7b-45e3-b62b-a52cc07fb450

Burgos, Elisa, Gomez-Nicola, Diego, Pascual, David, Martín, María Isabel, Nieto-Sampedro, Manuel and Goicoechea, Carlos (2012) Cannabinoid agonist WIN 55,212-2 prevents the development of paclitaxel-induced peripheral neuropathy in rats. Possible involvement of spinal glial cells. European Journal of Pharmacology. (doi:10.1016/j.ejphar.2012.02.008). (PMID:22374260)

Record type: Article

Abstract

Spinal glial activation contributes to the development and maintenance of chronic pain states, including neuropathic pain of diverse etiologies. Cannabinoid compounds have shown antinociceptive properties in a variety of neuropathic pain models and are emerging as a promising class of drugs to treat neuropathic pain. Thus, the effects of repeated treatment with WIN 55,212-2, a synthetic cannabinoid agonist, were examined throughout the development of paclitaxel-induced peripheral neuropathy. Painful neuropathy was induced in male Wistar rats by intraperitoneal (i.p.) administration of paclitaxel (1mg/kg) on four alternate days. Paclitaxel-treated animals received WIN 55,212-2 (1mg/kg, i.p.) or minocycline (15mg/kg, i.p.), a microglial inhibitor, daily for 14days, simultaneous with the antineoplastic. The development of hypersensitive behaviors was assessed on days 1, 7, 14, 21 and 28 following the initial administration of drugs. Both the activation of glial cells (microglia and astrocytes) at day 29 and the time course of proinflammatory cytokine release within the spinal cord were also determined. Similar to minocycline, repeated administration of WIN 55,212-2 prevented the development of thermal hyperalgesia and mechanical allodynia in paclitaxel-treated rats. WIN 55,212-2 treatment also prevented spinal microglial and astrocytic activation evoked by paclitaxel at day 29 and attenuated the early production of spinal proinflammatory cytokines (interleukin (IL)-1?, IL-6 and tumor necrosis factor (TNF)-?). Our results confirm changes in the reactivity of glial cells during the development of peripheral neuropathy induced by paclitaxel and support a preventive effect of WIN 55,212-2, probably via glial cells reactivity inactivation, on the development of this neuropathy.

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More information

e-pub ahead of print date: 21 February 2012
Keywords: paclitaxel, peripheral neuropathy, cannabinoid, hyperalgesia, cytokine, rat
Organisations: Biomedicine

Identifiers

Local EPrints ID: 333292
URI: https://eprints.soton.ac.uk/id/eprint/333292
ISSN: 0014-2999
PURE UUID: be82bd28-bb48-4212-b96e-423583c4da9c
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 06 Mar 2012 12:05
Last modified: 06 Jun 2018 12:33

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